Person: Sluss, Patrick M.
Loading...
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
Sluss
First Name
Patrick M.
Name
Sluss, Patrick M.
4 results
Search Results
Now showing 1 - 4 of 4
Publication CA125 Immune Complexes in Ovarian Cancer Patients with Low CA125 Concentrations(American Association for Clinical Chemistry (AACC), 2010) Cramer, Daniel; O'Rourke, D. J.; Vitonis, A. F.; Matulonis, Ursula; DiJohnson, D. A.; Sluss, Patrick M.; Crum, Christopher; Liu, B. C.- S.BACKGROUND About 20% of women with ovarian cancer have low concentrations of serum cancer antigen 125 (CA125), and this important tumor marker cannot be used to monitor their disease. The measured concentration for mucin 1 (MUC1), or CA15–3, another tumor marker, can be lowered in breast and ovarian cancer patients when circulating immune complexes (CICs) containing antibodies bound to the free antigen are present. Because CA125 and MUC1 are related members of the mucin family, we sought to determine whether CICs might also exist for CA125 and interfere with its clinical assay. METHODS We developed an antigen capture–based assay to determine the presence of CICs for CA125. We spotted mouse antibodies to CA125 onto nanoparticle slides, incubated them with patient serum, and added Cy5-tagged goat antihuman IgG antibodies. Fluorescence intensities were read and normalized to the intensities for glutathione S-transferase A1 as a control. RESULTS Assay results for 23 ovarian cancer cases with high CA125 concentrations, 43 cases with low CA125 concentrations, and 19 controls (mean CA125 concentrations, 2706, 23, and 11 kilounits/L, respectively) revealed mean fluorescence intensities for CA125 CIC of 2.30, 2.72, and 1.99 intensity units (iu), respectively. A generalized linear model adjusted for batch and age showed higher CA125 CIC fluorescence intensities in low-CA125 cases than in high-CA125 cases (P = 0.03) and controls (P = 0.0005). Four ovarian cancer patients who had recurrent disease and always had low CA125 values had a mean CA125 CIC value of 3.06 iu (95% CI, 2.34–4.01 iu). CONCLUSIONS These preliminary results suggest the existence of CICs involving CA125, which may help explain some ovarian cancer cases with low CA125 concentrations.Publication A Framework for Evaluating Biomarkers for Early Detection: Validation of Biomarker Panels for Ovarian Cancer(American Association for Cancer Research (AACR), 2011) Zhu, C. S.; Pinsky, P. F.; Cramer, Daniel; Ransohoff, D. F.; Hartge, P.; Pfeiffer, R. M.; Urban, N.; Mor, G.; Bast, R. C.; Moore, L. E.; Lokshin, A. E.; McIntosh, M. W.; Skates, Steven; Vitonis, A.; Zhang, Z.; Ward, D. C.; Symanowski, J. T.; Lomakin, A.; Fung, E. T.; Sluss, Patrick M.; Scholler, N.; Lu, K. H.; Marrangoni, A. M.; Patriotis, C.; Srivastava, S.; Buys, S. S.; Berg, C. D.A panel of biomarkers may improve predictive performance over individual markers. Although many biomarker panels have been described for ovarian cancer, few studies used pre-diagnostic samples to assess the potential of the panels for early detection. We conducted a multi-site systematic evaluation of biomarker panels using pre-diagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial. Using a nested case-control design, levels of 28 biomarkers were measured laboratory-blinded in 118 serum samples obtained before cancer diagnosis and 951 serum samples from matched controls. Five predictive models, each containing 6–8 biomarkers, were evaluated according to a pre-determined analysis plan. Three sequential analyses were conducted: blinded validation of previously established models (Step 1); simultaneous split-sample discovery and validation of models (Step 2); and exploratory discovery of new models (Step 3). Sensitivity, specificity, sensitivity at 98% specificity, and AUC were computed for the models and CA125 alone among 67 cases diagnosed within one year of blood draw and 476 matched controls. In Step 1, one model showed comparable performance to CA125, with sensitivity, specificity and AUC at 69.2%, 96.6% and 0.892, respectively. Remaining models had poorer performance than CA125 alone. In Step 2, we observed a similar pattern. In Step 3, a model derived from all 28 markers failed to show improvement over CA125. Thus, biomarker panels discovered in diagnostic samples may not validate in pre-diagnostic samples; utilizing pre-diagnostic samples for discovery may be helpful in developing validated early detection panels.Publication Ovarian Cancer Biomarker Performance in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Specimens(American Association for Cancer Research (AACR), 2011) Cramer, Daniel; Bast, R. C.; Berg, C. D.; Diamandis, E. P.; Godwin, A. K.; Hartge, P.; Lokshin, A. E.; Lu, K. H.; McIntosh, M. W.; Mor, G.; Patriotis, C.; Pinsky, P. F.; Thornquist, M. D.; Scholler, N.; Skates, Steven; Sluss, Patrick M.; Srivastava, S.; Ward, D. C.; Zhang, Z.; Zhu, C. S.; Urban, N.Establishing a cancer screening biomarker’s intended performance requires “phase III” specimens obtained in asymptomatic individuals before clinical diagnosis rather than “phase II” specimens obtained from symptomatic individuals at diagnosis. We used specimens from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial to evaluate ovarian cancer biomarkers previously assessed in phase II sets. Phase II specimens from 180 ovarian cancer cases and 660 benign disease or general population controls were assembled from four Early Detection Research Network (EDRN) or Ovarian Cancer Specialized Program of Research Excellence (SPORE) sites and used to rank 49 biomarkers. Thirty-five markers, including 6 additional markers from a fifth site, were then evaluated in PLCO proximate specimens from 118 women with ovarian cancer and 474 matched controls. Top markers in phase II specimens included CA125, HE4, transthyretin, CA15.3, and CA72.4 with sensitivity at 95% specificity ranging from 0.73 to 0.40. Except for transthyretin, these markers had similar or better sensitivity when moving to phase III specimens that had been drawn within six months of the clinical diagnosis. Performance of all markers declined in phase III specimens more remote than 6 months from diagnosis. Despite many promising new markers for ovarian cancer, CA125 remains the single-best biomarker in the phase II and phase III specimens tested in this study.Publication Genetic Variation in the Progesterone Receptor Gene and Ovarian Cancer Risk(Oxford University Press (OUP), 2005) Terry, Kathryn; De Vivo, Immaculata; Titus-Ernstoff, L.; Sluss, Patrick M.; Cramer, DanielEvidence suggests a role for progesterone in ovarian cancer development. Progesterone exerts its effect on target cells by interacting with its receptor. Thus, genetic variations that may cause alterations in the biologic functions of the progesterone receptor can potentially contribute to individual susceptibility to ovarian cancer. Using a population-based, case-control study, the authors genotyped four polymorphisms in the progesterone receptor gene (+44C/T, +331G/A, G393G, V660L) and inferred haplotypes in 987 ovarian cancer cases and 1,034 controls living in New Hampshire and eastern Massachusetts (May 1992–November 2002). Odds ratios and 95% confidence intervals were calculated to evaluate associations with ovarian cancer. No associations were observed between the +44C/T, +331G/A, and G393G polymorphisms and ovarian cancer. However, an inverse association was observed between the V660L variant and ovarian cancer (odds ratio = 0.70, 95% confidence interval: 0.57, 0.85). Associations remained after adjustment for potential confounders. Five haplotypes occurred with greater than 5% frequency, and the haplotype carrying the V660L variant had a significant association with ovarian cancer (odds ratio = 0.76, 95% confidence interval: 0.62, 0.92). Associations were similar after stratifying by ovarian cancer histologies and risk factors.